Poorly Differentiated Medullary Phenotype Predicts Poor Survival in Early Lymph Node-Negative Gastro-Esophageal Adenocarcinomas

PLoS One. 2016 Dec 28;11(12):e0168237. doi: 10.1371/journal.pone.0168237. eCollection 2016.

Abstract

Background: 5-year survival rate in patients with early adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in Caucasian patients is reported to be 60-80%. We aimed to identify prognostic markers for patients with UICC-I without lymph-node involvement (N0).

Methods: Clinical data and tissue specimen from patients with AGE/S stage UICC-I-N0, treated by surgery only, were collected retrospectively. Tumor size, lymphatic vessel or vein invasion, grading, classification systems (WHO, Lauren, Ming), expression of BAX, BCL-2, CDX2, Cyclin E, E-cadherin, Ki-67, TP53, TP21, SHH, Survivin, HIF1A, TROP2 and mismatch repair deficiency were analyzed using tissue microarrays and correlated with overall and tumor related survival.

Results: 129 patients (48 female) with a mean follow-up of 129.1 months were identified. 5-year overall survival was 83.9%, 5-year tumor related survival was 95.1%. Poorly differentiated medullary cancer subtypes (p<0.001) and positive vein invasion (p<0.001) were identified as risk factors for decreased overall-and tumor related survival. Ki-67 (p = 0.012) and TP53 mutation (p = 0.044) were the only immunohistochemical markers associated with worse overall survival but did not reach significance for decreased tumor related survival.

Conclusion: In the presented study patients with AGE/S in stage UICC-I-N0 had a better prognosis as previously reported for Caucasian patients. Poorly differentiated medullary subtype was associated with reduced survival and should be considered when studying prognosis in these patients.

MeSH terms

  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Medullary / mortality*
  • Carcinoma, Medullary / pathology
  • Carcinoma, Medullary / therapy
  • Cell Differentiation
  • Combined Modality Therapy
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Neoplasm Staging
  • Phenotype
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy
  • Survival Rate

Substances

  • Biomarkers, Tumor

Grants and funding

This study has been supported by a grant from “Berliner Krebsgesellschaft” (DAFF201101) (http://www.berliner-krebsgesellschaft.de). C. Treese is a participant in the Charité Clinical Scientist Program funded by the Charité—University Medicine Berlin and the Berlin Institute of Health (http://www.stiftung-charite.de/en/funding/private-excellence-initiative-johanna-quandt/bih-clinical-scientists.html).